Understanding the performance of the left ventricle requires not only examining the properties of the left ventricle itself, but also investigating the modulating effects of the arterial system on left ventricular (LV) performance. The interaction of the left ventricle with the arterial system, termed arterial-ventricular coupling, is a central determinant of cardiovascular performance and cardiac energetics. Arterial-ventricular coupling (EA/ELV) can be indexed by the ratio of effective arterial elastance (EA;a measure of the net arterial load exerted on the left ventricle) to LV end-systolic elastance (ELV;a load independent measure of LV chamber performance). At rest, in healthy individuals, EA/ELV is maintained within a narrow range, which allows the cardiovascular system to optimize energetic efficiency at the expense of mechanical efficacy. 1. Cardiac Performance at Rest and with Exercise: a longstanding project to measure cardiac volumes via Multi Gated Acquisition Scans (MUGA) at rest and with exercise, has been conducted over many years with multiple measures in individual BLSA participants. The study has now been completed with 341 total subjects and 154 subjects with multiple visits. Analysis is ongoing. 2. Arterial-Ventricular Coupling with Exercise: Resting EA/ELV did not differ between old (70 yr) and young (30 yr) subjects (n=25) because of an increase in EA and ELV in older subjects (Chantler 2009). During exercise, an acute mismatch between the arterial and ventricular systems occurs, due to a disproportionate increase in ELV (from an average of 4.3 to 13.2, and 4.7 to 15.5 mmHg/ml in men and women, respectively) vs. EA (from an average of 2.3 to 3.2, and 2.3 to 2.9 mmHg/ml in men and women, respectively), to ensure that sufficient cardiac performance is achieved to meet the increased energetic requirements of the body. As a result EA/ELV decreases from an average of 0.58 to 0.34, and 0.52 to 0.27 in men and women, respectively. However, with advancing age the reduction in EA/ELV from rest to peak exercise is blunted in older men and women, because of a deficit in the ability to augment ELV during exercise. 3. Arterial-Ventricular Interaction in the Presence of Nitroprusside: Sodium nitroprusside is a clinically available vasodilating agent that is primarily used in patients with congestive heart failure or with hypertensive crises. Sodium nitroprusside is considered a balanced vasodilator, because, at rest, it lowers LV preload by increasing venous capacitance, and it lowers arterial afterload predominantly by decreasing peripheral vascular resistance. In the heart, sodium nitroprusside enhances LV relaxation through a cGMP-mediated pathway, and it can also increase contractility through a cGMP-independent pathway. We evaluated the effects of sodium nitroprusside on EA/ELV and its components at rest and during graded exercise. Sodium nitroprusside and saline placebo were administered to 15 older (70+/-8years) and 9 younger (31+/-4years) healthy subjects on separate days. EA/ELV was non-invasively characterized as end-systolic volume (ESV)/stroke volume (SV), EA=end-systolic pressure (ESP)/SV, and ELV=ESP/ESV. At rest, in the older and younger groups, sodium nitroprusside respectively lowered EA by 10% (p<0.05) and 4% (p=NS), increased ELV by 47% and 27% (p<0.01), and thus reduced EA/ELV by 31% and 27% (p<0.01) compared to placebo. At peak exercise, sodium nitroprusside did not significantly influence EA in either age group. However, sodium nitroprusside increased ELV by 68% (p<0.01) and 46% (p<0.07) in the older and younger groups respectively, and thus reduced EA/ELV by 36% and 22% (p<0.001) compared to placebo. Importantly, the age-associated deficit in EA/ELV during exercise was attenuated by sodium nitroprusside. Examination of EA/ELV and its components has provided useful mechanistic insights into cardiovascular performance both at rest and during exercise. Sodium nitroprusside attenuates the age-associated deficits in peak EA/ELV, indicating that some of the age-associated deficits in cardiovascular performance during exercise are acutely reversible. In healthy individuals the changes in EAI during exercise are determined by distinct patterns of changes in arterial properties that are coupled to specific patterns of change in cardiac parameters. These findings suggest a cross-talk among large and small vessels and cardiac volumes and function, and provide novel insights into the dynamic cardiovascular alterations during exercise.